Expression analysis on 14-3-3 proteins in regenerative liver following partial hepatectomy

Abstract

Abstract14-3-3 proteins play a vital part in the regulation of cell cycle and apoptosis as signaling integration points. During liver regeneration, the quiescent hepatocytes go through hypertrophy and proliferation to restore liver weight. Therefore, we speculated that 14-3-3 proteins regulate the progression of liver regeneration. In this study, we analyzed the expression patterns of 14-3-3 proteins during liver regeneration of rat to provide an insight into the regenerative mechanism using western blotting. Only four isoforms (γ, ε, σ and τ/θ) of the 14-3-3 proteins were expressed in regenerative liver after partial hepatectomy (PH). The dual effects, the significant down-regulation of 14-3-3ε and the significant up-regulation of 14-3-3τ/θ at 2 h after PH, might play particularly important roles in S-phase entry. The significant peaks of 14-3-3σ at 30 h and of ε and τ/θ at 24 h might be closely related not only to the G2/M transition but also to the size of hepatocytes. Possibly, the peak of 14-3-3ε expression seen at 168 h plays critical roles in the termination of liver regeneration by inhibiting cellular proliferation.

YWHAE as an HE4 interacting protein can influence the malignant behaviour of ovarian cancer by regulating the PI3K/AKT and MAPK pathways

“…Moreover, YWHAE has been identified as an important element in human retinal photoreceptor rod cells [ 23 ], and is involved in the differentiation of adipose-derived mesenchymal stem cells into osteoblasts, thus enhancing the body’s osteogenic ability [ 24 ]. In contrast, some studies have detected a peak in YWHAE expression 168 h following partial liver resection, preventing cell cycle progression and negatively regulating liver regeneration [ 25 ]. These discordant findings therefore suggest that YWHAE may have a two-way regulatory effect on the cell cycle.…”

YWHAE Influences the Malignant Behaviour of Ovarian Cancer by Regulating the PI3K/AKT and MAPK Pathways Via HE4

“…Some researchers have found that YWHAE is also involved in the differentiation of adiposederived mesenchymal stem cells into osteoblasts, enhancing the body's osteogenic ability [24]. In contrast, some studies have detected a peak of YWHAE expression 168 h after partial liver resection, preventing cell cycle and negatively regulating liver regeneration [25]. Therefore, these discordant ndings suggest that YWHAE may have a two-way regulatory effect on the cell cycle.…”

Binding Partners of 14-3-3 (YWHA) Protein Isoforms among Mammalian Species, Tissues, and Developmental Stages

“…Binding of 14-3-3 sigma to the cyclin dependent kinases CDK2 and CDK4 also prevents entry into the S phase. Conversely, 14-3-3 proteins can also bind to the CDK inhibitor p27 which causes cell cycle progression [2]. The progression from G2 to M phase is paused by the interaction between 14-3-3 and CDC25C, also by keeping it in the cytoplasm, preventing CDC2 dephosphorylation, and creating a G2/M checkpoint [2].…”

“…Conversely, 14-3-3 proteins can also bind to the CDK inhibitor p27 which causes cell cycle progression [2]. The progression from G2 to M phase is paused by the interaction between 14-3-3 and CDC25C, also by keeping it in the cytoplasm, preventing CDC2 dephosphorylation, and creating a G2/M checkpoint [2]. Following that checkpoint, CDC25C can dephosphorylate and activate CDC2 which initiates entry into M phase.…”

“…In mammals, there are seven 14-3-3 isoforms that are encoded by separate genes and named according to Greek alphabets: beta (β), epsilon (ε), eta (η), gamma (γ), sigma (σ), tau/theta (τ/θ), and zeta (ζ). These proteins have been shown to interact with over 700 other proteins [1], allowing them to regulate diverse physiological processes such as the cell cycle, cell differentiation, and apoptosis [2]. These binding interactions involving the 14-3-3 proteins occur across all mammalian species, differing on the basis of cell types, tissues, organs, and developmental stages.…”